Content developed by Marie Fuzzati (IRCCS Mondino Foundation and France Parkinson) and Ludivine Breger (INSERM), in close collaboration with MIUR. For more information or for questions, please contact experimentalmodels@jpnd.eu.

General information

Mice: C57BL/6

Expression of the full-length human mutant (G2019S) LRRK2 protein, under the control of a hindbrain selective prion promoter and the mouse Thy1-regulatory sequences.

Endogenous LRRK2: yes

Corresponding human genotype: The G2019S substitution in the LRRK2 gene is believed to be the most common mutation associated with Parkinson’s disease. It is located in the kinase domain of the protein.

Transgene expression

5-7 months: The human transgene is expressed in the striatum, cortex, hippocampus, cerebellum and brainstem but is not detectable in the SN.

Neurodegeneration

Up to 19 months: No obvious neurodegeneration is observed.

Dopamine Homeostasis

Not reported

Inclusions

Up to 15 months: No differences in the levels of alpha-synuclein (phosphorylated or not) or Tau (Phosphorylated or not) are observed in the brain of transgenic animals.

Motor Behaviours

3-7 months: Transgenic animals seem to perform slightly better on the accelerating rotarod than the control littermates, however, the effect is only seen at a young age (3-4 months) and is only significant in the male cohort (Enhanced performance does not reach statistical significance in female). Similarly, the LRRK2G2019S animals travel longer distance than the wild type mice at 7 months. However, not difference can be observed in cocaine-induced hyperlocomotion, performances in the open field or on a running wheel.

10 months: Improved motor performances observed in young transgenic mice is lost with aging of the animals.

Response to dopaminergic treatment

Not reported

Non-motor Behaviours

2-4 months: No difference is observed in term of anxiety or learning abilities (open field, the dark/light box, elevated plus-maze or Morris watermaze).

Electrophysiology

Not reported

Neuroinflammation

6-12 months: No differences in the number of glial cells are observed.

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases, in particular Alzheimer’s. Learn More